Reduction of GABAA receptor-mediated inhibition by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione in cultured neurons of rat brain

The action of the non-N-methyl-d-aspartate (non-NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on γ-aminobutyric acid-A (GABAA) receptor-mediated currents was studied in dissociated rat midbrain and hypothalamic cultures using whole-cell recording. Spontaneous synaptic activit...

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Hauptverfasser: Jarolimek, Wolfgang (VerfasserIn) , Misgeld, Ulrich (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 1991
In: Neuroscience letters
Year: 1991, Jahrgang: 121, Heft: 1, Pages: 227-230
ISSN:1872-7972
DOI:10.1016/0304-3940(91)90691-L
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/0304-3940(91)90691-L
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/030439409190691L
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Verfasserangaben:W. Jarolimek and U. Misgeld

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520 |a The action of the non-N-methyl-d-aspartate (non-NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on γ-aminobutyric acid-A (GABAA) receptor-mediated currents was studied in dissociated rat midbrain and hypothalamic cultures using whole-cell recording. Spontaneous synaptic activity consisted of excitatory (EPSCs) and inhibitory postsynaptic currents (IPSCs). Bicuculline (20 μM) blocked IPSCs and increased the frequency of EPSCs. CNQX (1 μM) reduced both EPSCs and IPSCs. In the presence of 0.3 μM tetrodotoxin (TTX), CNQX (1-20 μM) blocked miniature EPSCs and reduced IPSCs. In TTX, increasing K+ (20 mM) evoked EPSCs and IPSCs in a Ca-dependent manner. CNQX (10 μM) blocked evoked EPSCs and diminished evoked IPSCs similarly as miniature IPSCs. Muscimol-(0.2-5 μM) induced currents were dose-dependently reduced by CNQX (10-50 μM). It is concluded that CNQX reduces GABAA receptor-mediated inhibition primarily by reducing the excitatory drive in the evolving network, but, in addition, has a significant blocking effect on the GABAA receptor-channel complex. 
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